Taste Masking

Taste masked products developed from innovative pharmaceutical

technologies increase the commercial profits and create brand

value for a company.

“bitter taste better”,

1. The flavor of a substance is attributed to its taste, sight, odor and qualities such as mouth feel.

2. Taste refers to a perception arising from the stimulation of taste buds present on the surface of the tongue.

3. Humans can distinguish among five components of taste: sourness, saltiness, sweetness, bitterness, and umami (savory)

Taste Masking

Taste masking technology filed in the period of year 1997 to 2007

Taste Masking

Trend of taste masking technology filed in the period of year 1997 to 2007

Taste Masking

It is one of the most efficient and commonly used taste masking technologies.

Coating

Coating can be done for tablets or for granules to be compressed into tablets, filled in capsules or suspended in a suspension

Coating

hydrophilic polymers: hydroxyethyl cellulose hydroxypropyl methylcellulose copovidone (PVP) polyvinyl alcohol

enteric polymers: cellulose acetate phthalate

water insoluble polymers : ethylcellulose polyvinyl acetate crospovidone croscarmellose

reverse enteric polymer: Eudragit EPO Eudragit E100

Lipophilic vehicles: vaseline and silicon oil for soft gel capsules

Coating

Lipids: glyceryl palmitostearate Stearic acid

gastrosoluble pore-formers: inorganic or organic salts (calcium carbonate or magnesium oxide)

Water soluble organic acids : tartaric acid used with hydrophilic polymers to promote salivation to facilitate the formation of a viscous and mouldable particle paste to ease the swallowing of coated particles.

Overcomes coating imperfections especially for aggressively bitter drugs.

Multilayer coating

water soluble polymer

a mixture of water soluble & insoluble polymers

to attain a balance between the taste masking and in vitro release in solid dosage forms

water insoluble polymer

enteric polymer

Overcomes coating imperfections especially for aggressively bitter drugs.

Multilayer coating

a combination of enteric and reverse enteric polymers With pH independent polymer used for liquid suspensions with the pH maintained between 3.5 and to prevent the dissolution of polymers. This approach can provide an efficient taste masked suspensions over a long storage time.

Overcomes coating imperfections especially for aggressively bitter drugs.

Multilayer coating

Spacing layer (EC:PVP)

Taste masking layer (Eudragit E 100)

spacing layer overcomes the compatibility issues between the drug and excipients and can reduce the coating imperfections thereby improving the taste masking efficiency.

Overcomes coating imperfections especially for aggressively bitter drugs.

Multilayer coating

a mixture of water soluble & insoluble polymers

saliva-insoluble polymer

sugar coating

hydroxyalkyl cellulose and an antitackiness agent

a sugar and a antitackiness agent

Methacrylate copolymer, a hydroxyalkyl cellulose & an antitackiness agent

Overcomes coating imperfections especially for aggressively bitter drugs.

Multilayer coating

cosmetic color coat

Water soluble organic acids and their salts such as tartaric acid can be used with hydrophilic polymers coating. They promote salivation to facilitate the formation of a mouldable viscous mass with a slippery surface in contact with the saliva that considerably facilitates the swallowing of the composition even in high doses

Sweeteners can be included in the coating solution for a better taste masking.

Acidic compounds such as citric and malic acid can be added to create an acidic microenvironment to promote the drug release in the upper

intestine from the particles coated with reverse enteric polymers range.

Blend of water insoluble polymer (polyvinyl acetate) and a gastrosoluble polymer (aminoalkyl methacrylate copolymer) to achieve taste masking & fast drug release

Coating

Granulation is an affordable, rapid and an easily scalable taste masking technology.

Granulation

Granulation

Drug + granulating agent

granulation taste masked granules

wet dry melt dry

syrup Suspension

Tablets

conventional

Chewable

dispersible

Swellable insoluble polymers

flavors wax

pH dependent Eudragit E-100

pH independent

Cation exchange resins

waxes: glycerol palmitostearate glyceryl behenate hydrogenated castor oil beeswax swelling polymers (During granulation, particle coating may remain incomplete. So, a swelling matrix can reduce the overall diffusion of the bitter active): Microcrystaline cellulose polycarbophil

Flavors: sugar alcohol (erythritol)

Granulation

Microencapsulation

Spray congealing

Spray drying

Solvent evaporation

Methods of preparation

phase separation (coacervation)

solvent extraction

Controlled release

Converting liquid to dry state

Taste masking

Applications

protection

Microencapsulation

Microencapsulation is an advantageous taste masking strategy for suspensions due to the low particle size distribution of microcapsules that can remain suspended for a longer time. The technique can be efficiently used for applying higher coating levels.

Coating materials used in particulate coating are also commonly used for microencapsulation.

Sweeteners

Sweeteners are commonly used in combination with other

taste masking technologies. They can be mixed with bitter

taste medicaments to improve the taste of the core

material which is prepared for further coating or may be

added to the coating liquid.

Sweeteners

Sugars: raw sgar, glucose and caramel sugar alcohol (sorbitol, xylitol, lactitol, maltitol or erythritol) sweeteners derived from plant parts Stevia glycyrrhizin Non sucrose component of sugar beet extract Synthetic sweeteners Sucralose improves taste without unpleasant, bitter/metallic taste or after-taste Stable in the presence of hemostatic or dental etching agents(acidic environment) compared to aspartame Less residue removed from the patient's tooth compared to sugar Shows synergy of bitter taste masking effectiveness at Low pH (2 to 5) Aspartame saccharin sodium acesulfame potassium cyclamate saccharin

glucose caramel sucrose

Sugars

maltitol lactitol erythritol

Sugar alcohol

xylitol sorbitol

glycyrrhizin

Non sucrose component of sugar beet extract

stevia

Sweeteners of plant sources

Sweeteners

saccharin Na

acesulfame K

Aspartame

Synthetic sweeteners

cyclamate Sucralose

50-60 > sucrose

after-taste perception flavor improving agent

Honey leaf

Cooling & warming agents Suppressants Blockers

Bitter taste blockers

Taste Suppressants and Potentiators

compete with bitter substances to bind with the G-protein

coupled (GPCR) receptor sites.

phospholipids

Lipoproteins

suppress unpleasant taste of medicament by subjecting taste receptors to extreme sensations

to overpower the bitter taste and confuse the brain.

warming cooling

eucalyptol methyl salicylate sweet and fruity compound

do not have their own taste & work at very low

concentration

Hydroxyflavanones their salts and stereoisomers

Taste Suppressants and Potentiators

Potentiators

increase the perception of the taste of sweeteners

and mask the unpleasant after taste.

Examples Thaumatine neohesperidine Dihydrochalcone (NHDC) glycyrrhyzin Aldehydes (citral dimethyl acetal & henylacetaldehyde dimethylacetal)

Solid dispersion

Taste masking

interactions between the drug & hydrophobic

polymers to decrease the solubility of a drug

Applications

interactions between poorly soluble drugs

and hydrophilic polymers to increase the solubility of the

drug

Natural polymers shellac and zein

long chain fatty acids stearic & palmitic acid Hydrophobic polymers

enteric polymers derivatives of acrylic acid polymers phthalate

This approach usually requires a higher concentration of excipients compared to

other taste masking techniques

Solid dispersion

Ion Exchange Resins

Are high molecular weight polymers with cationic and

anionic functional groups. Resins form insoluble

resinates through weak ionic bonding with oppositely

charged drugs. After ingestion, the resinate exchange

the drug with the counter ion in gastrointestinal tract

and the drug is eluted to be absorbed

Example: Amberlite

Complex Formation

Sweetners Cyclodextrins •wraps the bad tasting molecule to inhibit its interaction with the taste buds •interacts with the gatekeeper proteins of the taste buds

such as acesulfame

Adsorbates

The drug may be adsorbed or/and entrapped in the

matrix of the porous component, which may result in a

delayed release of the bitter active during the transit

through the oral cavity thereby achieving taste masking.

Viscosity Enhancers

Added to help masking highly bitter taste of suspended drug coated particles or microcapsules in liquid oral suspensions.

Mechanism of action: •retard the migration of dissolved drug from the surface of the solid particle to the suspending medium. •decrease the contact between the bitter medicament and the taste receptors

Examples: xanthan gum, microcrystalline cellulose, Na carboxymethylcellulose, Hypromellose

pH Modifiers

pH Modifying agents are capable of generating a

specific pH microenvironment in aqueous media that

can facilitate in situ precipitation of the bitter drug

substance in saliva thereby reducing the overall taste

sensation for liquid dosage forms like suspension.

Factors Affecting Selection of Taste Masking Technology

1. Extent of Bitter Taste

2. Dose of Active Pharmaceuticals

3. Drug Particle Shape and Size Distribution

4. Dosage Forms

5. Drug Solubility

6. Ionic Characteristics of the Drug

Organoleptic properties

Sensory panel test

Taste Flavor

Type Level

-Human tester -Scale from 1 to 5 for example -measures should be taken to minimize bias in evaluation -Not recommended to use elevated temperatures

Organoleptic properties

Measures to minimize bias in evaluation

-Determination of organoleptic capacity of the tester

-Ability to describe the flavor well

-Ability to duplicate results

-Ability to remember results

-Ability to detect new flavors (eg. Due to interaction with

container)

Electronic tongue is an instrument that measures and compares tastes.

Organoleptic properties

Mechanism involved for taste recognition in human and

electronic tongue shows the same three levels:

1. the receptor level [taste buds in humans, lipid

membrane of sensors in the electronic tongues]

2. the circuit level [neural transmission in humans,

transducers in the electronic tongues]

3. the perceptual level [cognition in the thalamus in

humans, statistical analysis by software in the

electronic tongues].

Electronic tongue

Organoleptic properties